Bone morphogenetic proteins (BMPs) and receptors (BMPR-1A, BMPR-1B, BMPR-2) have been shown to be vital for female reproduction, while their roles in males are poorly described. Our study was undertaken to specify the function of BMPR-1B in steroidogenic enzyme gene expression, testosterone production and reproductive development in male mice, given that Bmpr1b mRNA is expressed in mouse testis and Bmpr1b knockout results in compromised fertility. Male mice were passively immunized for 6 days with anti-BMPR-1B in the presence or absence of exogenous gonadotrophins. We then measured the effects of anti-BMPR-1B on testicular hydroxysteroid dehydrogenase isoforms (Hsd3b1, Hsd3b6, and Hsd17b3) and aromatase (Cyp19) mRNA expression, testicular and serum testosterone levels, and testis and seminal vesicle weight. In vitro testosterone production in response to anti-BMPR-1B was determined using testicular culture, and Leydig cell culture in the presence or absence of gonadotrophins. In Leydig cell culture the contribution of seminiferous tubules and Leydig cells were examined by preconditioning the media with these testicular constituents. In adult mice, anti-BMPR-1B increased testosterone and Hsd3b1 but decreased Hsd3b6 and Cyp19 mRNA. In adult testicular culture and seminiferous tubule conditioned Leydig cell culture, anti-BMPR-1B reduced testosterone, while in normal and Leydig cell conditioned Leydig cell culture it increased testosterone levels. In pubertal mice, anti-BMPR-1B reduced gonadotrophin stimulated seminal vesicle growth. In conclusion, BMPR-1B has specific developmental functions in the autocrine and paracrine regulation of testicular steroidogenic enzyme gene expression and testosterone production in adults and in the development of seminal vesicles during puberty.
- MeSH
- aromatasa metabolismus MeSH
- exprese genu MeSH
- kostní morfogenetické proteiny metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši MeSH
- pohlavní dospělost MeSH
- receptory kostního morfogenetického proteinu metabolismus MeSH
- testis * metabolismus MeSH
- testosteron * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aromatasa MeSH
- kostní morfogenetické proteiny MeSH
- messenger RNA MeSH
- receptory kostního morfogenetického proteinu MeSH
- testosteron * MeSH
In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.
- MeSH
- akrylamid toxicita MeSH
- apoptóza MeSH
- aromatasa * genetika MeSH
- furylfuramid MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- poměr pohlaví MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrylamid MeSH
- aromatasa * MeSH
- furylfuramid MeSH
Triazoles are used as antifungal agents, they mostly inhibit two enzymes: 14α-demethylase and aromatase. These enzymes are utilised also in other species and therefore the affection in non-target species in the environment is expected as well. Besides, triazoles are often being applied in a mixture and they can also interact with other substances present. This study clarifies how three selected representative triazoles (tebuconazole, penconazole and cyproconazole) interact with each other (group effect) and in mixtures (cocktail effect) with copper, essential/toxic for all organisms. Within the experiments on electrospray and collision-induced dissociations (both ESI-MS), it has been found that the fragments correspond to typical triazole metabolites. For their formation, the presence of copper ions is crucial. The inhibitory effect of Cu cocktails on aromatase enzymatic activity has been studied. The presence of Cu ions together with triazole(s) significantly increases the inhibitory effect on aromatase activity. The highest inhibitory effect (more than 60%) on aromatase activity is produced by cocktails containing penconazole and Cu ions, namely by penconazole/Cu and penconazole/tebuconazole/Cu. The reactivity of triazoles in groups is not significantly affected by the interactions among them. Additionally, the role of triazoles in copper Fenton reaction regulation has been observed and described. These changes may be attributed to the formation and stabilization of the complexes with the central Cu ion, with usually one, two or three triazolic ligands, depending on the mixture. The study demonstrates that the interaction of triazoles and Cu ions is a complex process; their impact on metabolism seems to be rather extensive and must be evaluated in the context of biochemical reactions.
- Klíčová slova
- Azoles, Cocktail effect, Cytochrome P450 monooxygenases, Fenton reaction,
- MeSH
- antifungální látky MeSH
- aromatasa * MeSH
- měď * MeSH
- oxidace-redukce MeSH
- triazoly MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antifungální látky MeSH
- aromatasa * MeSH
- měď * MeSH
- triazoly MeSH
The crucial role that oestrogens play in male reproduction has been generally accepted; however, the exact mechanism of their action is not entirely clear and there is still much more to be clarified. The oestrogen response is mediated through oestrogen receptors, as well as classical oestrogen receptors' variants, and their specific co-expression plays a critical role. The importance of oestrogen signalling in male fertility is indicated by the adverse effects of selected oestrogen-like compounds, and their interaction with oestrogen receptors was proven to cause pathologies. The aims of this review are to summarise the current knowledge on oestrogen signalling during spermatogenesis and sperm maturation and discuss the available information on oestrogen receptors and their splice variants. An overview is given of species-specific differences including in humans, along with a detailed summary of the methodology outcome, including all the genetically manipulated models available to date. This review provides coherent information on the recently discovered mechanisms of oestrogens' and oestrogen receptors' effects and action in both testicular somatic and germ cells, as well as in mature sperm, available for mammals, including humans.
- Klíčová slova
- humans, mice, oestrogen receptors, oestrogen-like compounds, oestrogens, pigs, rats, signalling, sperm, testes,
- MeSH
- aromatasa nedostatek genetika MeSH
- estrogeny farmakologie MeSH
- lidé MeSH
- receptory pro estrogeny metabolismus MeSH
- signální transdukce MeSH
- spermatogeneze účinky léků MeSH
- testis účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- aromatasa MeSH
- estrogeny MeSH
- receptory pro estrogeny MeSH
Bisphenol A (BPA), a chemical component of plastics, is a widely distributed environmental pollutant and contaminant of water, air, and food that negatively impacts human health. Concerns regarding BPA have led to the use of BPA-free alternatives, one of which is bisphenol S (BPS). However, the effects of BPS are not well characterized, and its specific effects on reproduction and fertility remain unknown. It is therefore necessary to evaluate any effects of BPS on mammalian oocytes. The present study is the first to demonstrate the markedly negative effects of BPS on pig oocyte maturation in vitro, even at doses lower than those humans are exposed to in the environment. Our results demonstrate (1) an effect of BPS on the course of the meiotic cell cycle; (2) the failure of tubulin fibre formation, which controls proper chromosome movement; (3) changes in the supply of maternal mRNA; (4) changes in the protein amounts and distribution of oestrogen receptors α and β and of aromatase; and (5) disrupted cumulus cell expansion. Thus, these results confirm that BPS is an example of regrettable substitution because this substance exerts similar or even worse negative effects than those of the material it replaced.
- MeSH
- aromatasa genetika MeSH
- buněčná diferenciace účinky léků genetika MeSH
- fenoly farmakologie MeSH
- meióza účinky léků MeSH
- messenger RNA genetika MeSH
- oocyty cytologie účinky léků metabolismus MeSH
- prasata MeSH
- receptory pro estrogeny genetika MeSH
- sulfony farmakologie MeSH
- vývojová regulace genové exprese účinky léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aromatasa MeSH
- bisphenol S MeSH Prohlížeč
- fenoly MeSH
- messenger RNA MeSH
- receptory pro estrogeny MeSH
- sulfony MeSH
Granulosa cell (GC) expressed androgen receptors (AR) and intrafollicular androgens are central to fertility. The transactivating domain of the AR contains a polymorphic CAG repeat sequence, which is linked to the transcriptional activity of AR and may influence the GC function. This study aims to evaluate the effects of the AR CAG repeat length on the intrafollicular hormone profiles, and the gene expression profiles of GC from human small antral follicles. In total, 190 small antral follicles (3-11 mm in diameter) were collected from 58 women undergoing ovarian cryopreservation for fertility preservation. The biallelic mean of the CAG repeat lengths were calculated for each woman, and grouped in three groups: Long CAG repeats (23-26 mean CAG); medium CAG repeats (20.5-22.5 mean CAG) and short CAG repeats (17.5-20.0 mean CAG). The following parameters were measured: follicle diameter, intrafollicular levels of Anti-Müllerian Hormone (AMH), progesterone, oestradiol, testosterone and androstenedione, and GC gene expression levels of FSHR, LHR, AR, CYP19A1, and AMH. The long CAG repeat lengths were associated with significantly decreased testosterone levels, as compared to medium CAG repeats (P = 0.05) and short CAG repeats (P = 0.003). Furthermore, in follicles 3-6 mm in diameter, the long CAG repeats were associated with significantly increased LHR and CYP19A1 gene expression levels compared to short CAG repeat lengths (P = 0.004 and P = 0.04 respectively), and significantly increased LHR expression compared to medium CAG repeat lengths (P = 0.03). In conclusion, long CAG repeat lengths in the AR were associated to significant attenuated levels of androgens and an increased conversion of testosterone into oestradiol, in human small antral follicles.
- Klíčová slova
- Androgen levels, Androgen receptor, CAG repeats, Follicular fluid, Human small antral follicles,
- MeSH
- androgenní receptory genetika MeSH
- aromatasa genetika MeSH
- dospělí MeSH
- expanze trinukleotidových repetic * MeSH
- folikulární tekutina cytologie metabolismus MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pohlavní hormony genetika metabolismus MeSH
- receptory LH genetika MeSH
- stanovení celkové genové exprese metody MeSH
- testosteron metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- androgenní receptory MeSH
- AR protein, human MeSH Prohlížeč
- aromatasa MeSH
- CYP19A1 protein, human MeSH Prohlížeč
- pohlavní hormony MeSH
- receptory LH MeSH
- testosteron MeSH
The fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100, 400 and 800 μg/L VZ and 5 μg/L 17β-estradiol (E2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 μg/L VZ, while it was increased in goldfish exposed to 100 μg/L VZ after 30 days of exposure. Circulating E2 level was unchanged in VZ treated goldfish, however the E2/11-KT ratio was increased in a concentration-related manner. In E2 treated goldfish, circulatory 11-KT and E2 levels were decreased and increased, respectively, which resulted in an increase in the E2/11-KT ratio. Exposure to VZ at 100 μg/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3β-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish.
- Klíčová slova
- Cytochrome P450 aromatase, Gonadotropin-releasing hormone, Luteinizing hormone, Sex steroids, Steroidogenic enzyme genes,
- MeSH
- aromatasa metabolismus MeSH
- chemické látky znečišťující vodu aplikace a dávkování toxicita MeSH
- estradiol metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- hypofýza účinky léků metabolismus MeSH
- játra účinky léků metabolismus MeSH
- karas zlatý * MeSH
- oxazoly aplikace a dávkování toxicita MeSH
- rozmnožování účinky léků fyziologie MeSH
- testis účinky léků metabolismus MeSH
- vitelogeniny metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aromatasa MeSH
- chemické látky znečišťující vodu MeSH
- estradiol MeSH
- hormon uvolňující gonadotropiny MeSH
- oxazoly MeSH
- vinclozolin MeSH Prohlížeč
- vitelogeniny MeSH
Adverse effects of bisphenol A (BPA) on reproductive physiology were studied in male goldfish (Carassius auratus) exposed to nominal environmentally relevant concentrations (0.2 and 20 µg/L) for up to 90 d. Transcriptions of various reproductive genes were measured in brain, liver, and testis to investigate the BPA modes of action. Volume, density, total number, motility, and velocity of sperm were measured to assess testicular function. At 0.2 µg/L, BPA reduced steroidogenetic acute regulatory protein and increased estrogen receptors (ERs) messenger RNA (mRNA) transcript (ERβ1 in liver and ERβ2 in testis) after 90 d. At 20 µg/L, BPA increased mRNA transcript of androgen receptor in testis, brain- and testis-specific aromatase, and vitellogenin in liver after 90, 30, 60, and 60 d, respectively. Transcripts of ERs mRNA were increased after 30 to 60 d at 20 µg/L BPA; increase in ERβ1 mRNA was observed in testis after 7 d. Total number, volume, and motility of sperm were decreased in males exposed to 0.2 and 20 µg/L BPA, whereas sperm density and velocity were only reduced at 20 µg/L BPA. The results support the hypothesis that BPA may exert both anti-androgenic and estrogenic effects, depending on concentration, leading to diminished sperm quality. The findings provide a framework for better understanding of the mechanisms mediating adverse reproductive actions of BPA observed in different parts of the world.
- MeSH
- androgenní receptory genetika metabolismus MeSH
- androgeny metabolismus MeSH
- aromatasa genetika metabolismus MeSH
- benzhydrylové sloučeniny toxicita MeSH
- estrogeny metabolismus MeSH
- fenoly toxicita MeSH
- karas zlatý MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- motilita spermií účinky léků MeSH
- orgánová specificita MeSH
- receptory pro estrogeny genetika metabolismus MeSH
- rozmnožování účinky léků genetika MeSH
- spermie cytologie účinky léků fyziologie MeSH
- testis cytologie účinky léků fyziologie MeSH
- testosteron metabolismus farmakologie MeSH
- vitelogeniny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- androgenní receptory MeSH
- androgeny MeSH
- aromatasa MeSH
- benzhydrylové sloučeniny MeSH
- bisphenol A MeSH Prohlížeč
- estrogeny MeSH
- fenoly MeSH
- látky znečišťující životní prostředí MeSH
- messenger RNA MeSH
- receptory pro estrogeny MeSH
- testosteron MeSH
- vitelogeniny MeSH
Hyperandrogenic states in pregnancy are almost always the result of a condition that arises during pregnancy. The onset of virilization symptoms is often very fast. The mother is protected against hyperandrogenism by a high level of SHBG, by placental aromatase and a high level of progesterone. The fetus is protected from the mother's hyperandrogenism partly by the placental aromatase, that transforms the androgens into estrogens, and partly by SHGB. Nevertheless there is a significant risk of virilization of the female fetus if the mother's hyperandrogenic state is serious. The most frequent cause of hyperandrogenic states during pregnancy are pregnancy luteoma and hyperreactio luteinalis. Hormonal production is evident in a third of all luteomas, which corresponds to virilization in 25-35 % of mothers with luteoma. The female fetus is afflicted with virilization with two thirds of virilized mothers. Hyperreactio luteinalis is created in connection with a high level of hCG, e.g. during multi-fetus pregnancies. This condition most frequently arises in the third trimester, virilization of the mother occurs in a third of cases. Virilization of the fetus has not yet been described. The most serious cause of hyperandrogenism is represented by ovarian tumors, which are fortunately rare.
- MeSH
- adenom kůry nadledvin diagnostické zobrazování metabolismus MeSH
- adrenokortikální karcinom diagnostické zobrazování metabolismus MeSH
- androgeny biosyntéza fyziologie MeSH
- aromatasa nedostatek MeSH
- dospělí MeSH
- hyperandrogenismus komplikace diagnostické zobrazování metabolismus MeSH
- komplikace těhotenství diagnostické zobrazování metabolismus MeSH
- lidé MeSH
- luteom diagnostické zobrazování metabolismus MeSH
- nadledviny diagnostické zobrazování metabolismus MeSH
- nádory nadledvin metabolismus MeSH
- nádory vaječníků diagnostické zobrazování metabolismus MeSH
- ovarium diagnostické zobrazování metabolismus MeSH
- placenta enzymologie MeSH
- plod metabolismus MeSH
- těhotenství MeSH
- ultrasonografie prenatální MeSH
- virilizace diagnostické zobrazování etiologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- androgeny MeSH
- aromatasa MeSH
Aromatase inhibitors are effective and well tolerated drugs in the endocrine therapy of estrogen-receptor positive breast cancer in postmenopausal women. Questions remain about the long-term side effects and safety profile of aromatase inhibitors. The results of ongoing studies may indicate the role of aromatase inhibitors in the prevention of breast cancer. The effectiveness and safety of aromatase inhibitor monotherapy in premenopausal breast cancer patients is unknown, so this is an area of future exploration. Our results in the chemoprevention of mammary carcinogenesis in female rats pointed to the potential favourable effects of aromatase inhibitors--anastrozole and letrozole in premenopausal women affected by breast cancer.
- MeSH
- aromatasa fyziologie MeSH
- inhibitory aromatasy terapeutické užití MeSH
- lidé MeSH
- nádory prsu farmakoterapie patofyziologie prevence a kontrola MeSH
- premenopauza * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- aromatasa MeSH
- inhibitory aromatasy MeSH
